Prevention of acetaminophen-induced hepatocyte injury: JNK inhibition and GSTA1 involvement

Abstract

Background

Glutathione S-transferase A1 (GSTA1) is a detoxification enzyme and a sensitive marker for hepatotoxicity. We investigated the effects of JNK inhibition on different degrees of Acetaminophen (APAP)-induced hepatocyte injury and GSTA1 expression.

Objective

This study aimed to investigate the role of JNK signaling pathway in APAP-induced different degrees of hepatocyte injury and its correlation with GSTA1 by inhibiting the phosphorylation of JNK by SP600125.

Results

6 and 8 mM APAP induced different degrees of hepatocyte injury and apoptosis, both activated JNK signaling pathway. In contrast, JNK inhibitor significantly reduced activation of JNK and c-JUN on exposure to APAP. Meanwhile, the levels of hepatocyte injury, oxidative stress, and apoptosis obviously decreased. Importantly, GSTA1 expression was significantly increased by JNK inhibition.

Conclusions

JNK inhibition attenuates APAP-induced hepatocyte injury and oxidative stress and increases GSTA1 expression. Furthermore, GSTA1 may be involved in this signaling pathway for detoxification.

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Acknowledgement

This work was supported by the National Natural Science Foundation of China (Grant Number 31472241).

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FL supervised the whole experiments. JH and YC performed the practical work and completed the experiments. YC and MI wrote the whole manuscript. BM, JW, RZ, LY JL, and CL provided help during the experiments.

Corresponding author

Correspondence to Fangping Liu.

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Cite this article

Chang, Y., He, J., Ma, B. et al. Prevention of acetaminophen-induced hepatocyte injury: JNK inhibition and GSTA1 involvement. Mol. Cell. Toxicol. (2021). https://doi.org/10.1007/s13273-021-00119-8

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Keywords

  • JNK
  • GSTA1
  • Acetaminophen
  • SP600125
  • Hepatocyte injury